Research The Pathogenesis Of Extracellular Matrix Remodeling With Cardiac Hypertrophy And Evaluation Of Left Ventricular Function

BackgroundsCardiac hypertrophy is associated with an increased risk of heart failure ,a major cause of death and disability.The accumulation of extracellular matrix(ECM) in the heart plays an important role in the development of cardiac hypertrophy. Myocyte hypertrophy and interstitial fibrosis in left ventricle(LV),refered to as remodeling contribute to development of depressed cardiac performance . Accordingly, it is of critical importance to understand the underlying mechanisms of cardiac hypertrophy and to develop therapeutic strategies that will effectively inhibit the development and progression of LV remodeling.Cardiac extracellular matrix (ECM ) consists of several groups of extracellular macromolecules. As a major component, cardiac collagen provides alignment to myocardial cells and serves as the skeleton of cardiac collagen network, Which maintains the ventricular chambers in normal structural architecture and function . The matrix metalloproteinases (MMPs)are a family of structurally related endopeptidases that have the ability to degrade all components of the extracellular matrix,so they are the major physiological regulators of theextracellular matrix. It has been shown that transforming growth factor B 1(TGF- B1) induces fibrosis and accumulation of extracellular matrix .Whether the cardiac remodeling process can be reversed and the potential mechanism are currently a topic of great research interest.Currently, the new echocardiography techniques of quantitative tissue velocity imaging strain and strain rate imaging could detect the regional systolic and diastolic function of the heart. Ultrasonic tissue characterization with measurement of backscatter has been employed in numorous experimental and clinical studies of cardiac pathology,yet the cellular components responsible for scattering from cardiac tissues have not been unequivocally identified.Objectives1. To investigate the role of metalloproteinase(MMP-9) and tissue inhibitor of metal loproteinase(TIMP-l) and transforming growth factor B 1(TGF- B1) in cardiac hypertrophy and extracellular matrix remodeling and effect of Losartan on it in a rat model.2. To study the effect and mechanisms of Atorvastatin in rats with norepinephrine-induced cardiac hypertrophy and extracellular matrix remodeling.3. To investigate the change of ultrasonic integrated backscatter(IBS) and the relations between IBS and cardiac extracellular matrix(ECM) remodeling and expression of matrix metalloproteinase(MMP-9) andtissue inhibitor of metalloproteinase(TIMP-1) in rats with norepinephrine - induced cardiac hypertrophy.4. To explore the regional systolic and diastolic function in patients with essential hypertension by the quantitative tissue velocity imaging strain and strain rate imaging. Methods1. Male SD rats were randomly divided into three groups: (1) control (n=8 ), (2 ) norepinephrine (1.06 mg kg1 d-1 x 15 d ) (n=8), (3 ) norepinephrine + Losartan( 10 mg kg-1 d-1 x 15 d) (n=9 ) . The rat models which were established by norepinephrine injectioned intraperitoneally twice a day for 15 days. Cardiac hypertrophy and extracellular matrix remodeling were evaluated by echocardiography and morphological examination .The mRNA and protein expression of matrix metalloproteinase(MMP-9) and tissue inhibitor ofmetalloproteinase(TIMP-l) and transforming growth factor B1(TGF-B1 )were examined by reverse transcription-polymerase chain reaction(RT-PCR) and immunohistochemical analysis.2.SD rats were randomly divided into three groups:(l)control(n=8),(2)norepinephrine(1.06mg kg-1 d-1 x15d)(n=8 ),(3)norepinephrine+Atorvastatin(50mg kg-1 d-1 x15d)(n=9). The collagen and mRNA and protein expression of MMP-9 TIMP-1 and TGF-B1 were evaluated by echocardiography morphologicalexamination and RT-PCR and immunohistochemical analysis.3. The rat models which was established by norepinephrine(NE 1.06 mg kg-1 d-1) injectioned intrape...